Mathematical modeling and computational biology are increasingly appreciated for their contribution to the analysis and understanding of practical biological and medical problems. With regard to HIV infection, for example, such approaches have been instrumental in generating testable hypotheses regarding viral persistence and evolution, in providing insights into dynamics and pathogenesis, and in the analysis of nucleotide sequence data to investigate viral escape from the selective pressure of immune responses and antiretroviral treatment. We propose to formalize and enhance what has proven to be several productive ad hoc collaborations in HIV research to establish a center for viral dynamics and evolution. This center will bring cerebrum to bench to bedside in one location. It will enhance and formalize existing ad hoc collaborations, it will bring the expertise of the UCSD Supercomputer Center into one HIV research program, it will establish training opportunities in mathematical studies in HIV/AIDS research and it will expand these studies to other chronic viral infections, specifically hepatitis B virus (HBV) and hepatitis C virus (HCV). AIM 1: To assemble theoretical and experimental investigators in a coordinated center. AIM 2: To apply modeling and analytic approaches to several important problems in chronic viral infection. Initial studies will focus on: a) Lymphocyte dynamics in acute HIV infection b) Nucleotide sequence analysis of HIV evolution under the selective pressures of drug treatment and immune responses c) HIV dynamics in the central nervous system d) Hepatitis C virus dynamics in HIV infected patients.